High-resolution mapping of chromatin packaging in mouse embryonic stem cells and sperm
Department of Biochemistry and Molecular Pharmacology; Program in Bioinformatics and Integrative Biology; Program in Gene Function and Expression; Department of Developmental and Cell Biology
Bioinformatics | Cell Biology | Computational Biology | Developmental Biology | Genetics and Genomics | Integrative Biology
Mammalian embryonic stem cells (ESCs) and sperm exhibit unusual chromatin packaging that plays important roles in cellular function. Here, we extend a recently developed technique, based on deep paired-end sequencing of lightly digested chromatin, to assess footprints of nucleosomes and other DNA-binding proteins genome-wide in murine ESCs and sperm. In ESCs, we recover well-characterized features of chromatin such as promoter nucleosome depletion and further identify widespread footprints of sequence-specific DNA-binding proteins such as CTCF, which we validate in knockdown studies. We document global differences in nuclease accessibility between ESCs and sperm, finding that the majority of histone retention in sperm preferentially occurs in large gene-poor genomic regions, with only a small subset of nucleosomes being retained over promoters of developmental regulators. Finally, we describe evidence that CTCF remains associated with the genome in mature sperm, where it could play a role in organizing the sperm genome.
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Citation: Carone BR, Hung JH, Hainer SJ, Chou MT, Carone DM, Weng Z, Fazzio TG, Rando OJ. High-resolution mapping of chromatin packaging in mouse embryonic stem cells and sperm. Dev Cell. 2014 Jul 14;30(1):11-22. doi: 10.1016/j.devcel.2014.05.024. Link to article on publisher's site